OBJECTIVE: To determine the hyperthermic modifying effect of selected extracellular environmental conditions on cultured mammalian cells. The relationship between hyperthermic lethality and the following conditions will be examined: 1) Oxygen tension, 2) Hydrogen ion concentration, 3) Nutritional deprivation, 4) The interrelationship of these factors. Specifically, the hyperthermic oxygen enhancement ratio will be determined and compared to the radiation oxygen enhancement ratio at selected oxygen concentrations. The response of cells to heat or radiation will be determined under acute and chronic hypoxic conditions. These experiments will be performed at selected elevated temperatures, 41-45 degrees C. Variable oxygen tensions will be obtained using a rapid gassing technique and low density cultures to eliminate nutritional deprivation and change in pH. The response of cells at selected hydrogen ion concentrations to elevated temperatures or X-irradiation will be determined under oxygenated and acute and chronic hypoxic conditions. Experiments will be designed to determine if nutritionally deprived plateau phase cells are relatively heat sensitive. The results will be evaluated with respect to changes in age distribution, pH, oxygen tension, and nutritional history. Numerous observations have demonstrated that the concentration of extracellular metabolites in normal and tumor tissues varies significantly. The effect of these factors on hyperthermic lethality will be identified and quantitatively evaluated. It is expected that the data obtained will provide a rationale for the use of hyperthermia to treat cancer which is based on naturally occurring differences between normal and tumor tissues.